Butyrate, a metabolite of intestinal bacteria, enhances sleep

Sci Rep. 2019 May 7;9(1):7035. doi: 10.1038/s41598-019-43502-1.


Emerging evidence suggests that the intestinal microbiota is a source of sleep-promoting signals. Bacterial metabolites and components of the bacterial cell wall are likely to provide important links between the intestinal commensal flora and sleep-generating mechanisms in the brain. Butyrate is a short-chain fatty acid produced by the intestinal bacteria by the fermentation of nondigestible polysaccharides. We tested the hypothesis that butyrate may serve as a bacterial-derived sleep-promoting signal. Oral gavage administration of tributyrin, a butyrate pro-drug, elicited an almost 50% increase in non-rapid-eye movement sleep (NREMS) in mice for 4 hours after the treatment. Similarly, intraportal injection of butyrate led to prompt and robust increases in NREMS in rats. In the first 6 hours after the butyrate injection, NREMS increased by 70%. Both the oral and intraportal administration of butyrate led to a significant drop in body temperature. Systemic subcutaneous or intraperitoneal injection of butyrate did not have any significant effect on sleep or body temperature. The results suggest that the sleep-inducing effects of butyrate are mediated by a sensory mechanism located in the liver and/or in the portal vein wall. Hepatoportal butyrate-sensitive mechanisms may play a role in sleep modulation by the intestinal microbiota.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Butyrates / administration & dosage
  • Butyrates / metabolism
  • Butyrates / pharmacology*
  • Butyric Acid / administration & dosage
  • Butyric Acid / pharmacology
  • Gastrointestinal Microbiome / physiology*
  • Injections
  • Mice, Inbred C57BL
  • Rats, Sprague-Dawley
  • Sleep / drug effects*
  • Sleep / physiology*
  • Triglycerides / administration & dosage
  • Triglycerides / pharmacology


  • Butyrates
  • Triglycerides
  • Butyric Acid
  • tributyrin